The interplay of circadian timing and metabolic physiology represents a new frontier in biomedical research. Research on weight gain in humans has focused primarily on macronutrient intake and energy expenditure, the latter predominantly through physical activity, to understand and treat overweight and obesity. Emerging evidence from animal models indicates that circadian physiology impacts weight gain, including the observation of obesity in clock gene mutants and most recently the finding that food intake restricted to the habitual sleep time of mice leads to weight gain as compared to the same amount of food intake during the normal wake episode. We propose to determine if findings from these mouse models translate to humans. To do so, we have designed an exploratory Clinical and Translational Research Center (CTRC) study that uses whole room calorimetry to determine how restricting the majority of food intake to the biological night impacts energy metabolism in humans. Eating at night is common in work schedules with long work hours and with work operations during the nighttime hours (e.g., health care, emergency response, security personnel) and in circadian sleep disorders including, but not limited to, shift work and jet lag disorder. Night eating disorders are also newly recognized conditions that may contribute to obesity. The project addresses several themes outlined in NIH PA NUMBER: 09-124 Exploratory/Developmental Clinical Research Grants in Obesity by testing the following specific hypothesis: i) circadian misalignment will lead to reduced fat oxidation-a physiological state that could contribute to weight gain. This research effort is responsive to PA-09-124 as it will assess how a behavioral phenotype of eating at night increases risk for obesity and will contribute to identification of this behavior as a modifiable determinant of overweight and obesity. PUBLIC HEALTH RELEVANCE: Shift work and jet lag as well as other circadian rhythm sleep disorders and night eating disorders are associated with negative health outcomes, including obesity, cardiovascular disease and diabetes. This research will determine whether eating at night alters physiological mechanisms that promote weight gain and obesity.